Functionalized chiral ketones, such as α-amino ketones, α,α′-diamino ketones, β-nitro ketones, and their derivatives, are prevalent building blocks and ubiquitous subunits present in natural products and pharmaceutical leads. The synthesis of chiral ketones can be achieved via direct α-substitutions. For example, the synthesis of α-amino ketones has been achieved via catalytic amination of ketones by diethyl diazenedicarboxylate (DEAD). Despite the success, some drawbacks of this method lie in the unsatisfactory and/or undesired regio-selectivities for unsymmetric ketones and to certain extent the demanding conditions required for subsequent N—N bond cleavages.
Recently, a metal-free nitrosobenzene mediated C—C bond cleavage for esters and 1,3-diketo compounds was developed. The C—C bond cleaving transformations for achiral aldehydes have been studied since the 1950s via oxidation of the corresponding preformed enamines in the presence of strong metal oxidants or catalysts. However, nearly all the reported reactions for C—C bond cleavage of aldehydes were sluggish with the formation of multiple side products (or even dominating undesired products) due to the non-selective conditions. Furthermore, these methods only deal with achiral and simple aldehydes bearing no useful functional groups.
Therefore, there remains a need to provide for methods to prepare functionalized chiral ketones in order to overcome, or at least alleviates, the above drawbacks.